Antibodies directed against idiotypic determinants on anti-Staphylococcal nuclease antibodies from different mouse strains have been produced in rats and in pigs. The idiotypes are detected by hemagglutination assays and by the inhibition of antibody-mediated inactivation of nuclease. By screening a variety of strains and offspring from appropriate mating between strains for the presence of idiotypes and other markers, it has been shown that idiotype expression is linked to the heavy chain allotype markers. By means of an in vitro anti-TNP nuclease plaque-forming cell response, idiotypic markers have been demonstrated on T helper cells. Administration of anti idiotypic antibodies to mice has been found to induce idiotype expression in the serum of these animals. This effect appears to involve T cells, since it is not observed in nude mice, and since idiotype-bearing T helper cells for in vitro anti-TNP nuclease response have been found in spleens from such treated an;imals. Isoelectric focusing studies on anti-nuclease antibodies have indicated characteristic spectrotypes for different strains which appear to correlate with idiotype expression. Several hybridomas reactive with nuclease and/or anti-idiotype have been produced.